1. Field of the Invention
The present invention relates to an apparatus and a method for the time-resolved and location-resolved evaluation of nuclear magnetic resonance signals acquired with the aid of nuclear magnetic resonance in order to detect activity changes in a life form, whereby physiological processes are stimulated in the life form by using at least two stimulation functions.
2. Description of the Prior Art
It has been determined that brain activities caused by stimulation can be detected in the cerebral cortex of human beings with a nuclear magnetic resonance tomography apparatus. A procedure producing and registering such brain activity is known as a stimulation experiment. Such stimulation experiments have been carried out with visual stimulation and with stimulation around the primary motor cortex, for example, by finger movement. Functional brain examinations also can be carried out by different techniques such as PET (positron emission tomography) or EEG. A significantly better topical resolution, however, can be obtained by nuclear magnetic resonance tomography.
An experiment that is typically carried out using nuclear magnetic resonance tomography is known as an BOLD-fMRI experiment. BOLD stands for Blood-Oxygen-Level Dependent (dependent on the oxygen content of the blood). Activity due to a stimulation in a tissue generates a temporary lack of oxygen in the blood surrounding the tissue. The organism detects this lack of oxygen. New oxygen is supplied via the surrounding blood vessels. Given a sudden activity in the tissue, the oxygen content is initially, temporarily, slightly reduced, followed by a long-term-decay overshoot of the oxygen content in the blood as a result of the automatic controller action of the organism. This chronological modification of the local oxygen content in the blood is measured and localized in BOLD-fMRI experiments (fMRI stands for functional magnetic resonance tomography) using a nuclear magnetic resonance tomography apparatus. As an example, FIG. 4 herein shows the chronological course of such a local oxygen concentration in the blood.
Given the acquisition of data in realtime, the time resolution is also limited as a result of the limited pickup speed of the nuclear magnetic resonance technique. Therefore, there are suggestions to trigger the acquisition of data for the functional imaging by stimulations. Only one part of the raw data required for a complete image dataset is acquired per stimulation. Therefore, it has been suggested to synchronize the data acquisition with a periodic repetition of a task triggering brain activities. A similar method has already been used for xe2x80x9cfilm pickupsxe2x80x9d of the heart movement.
A problem in functional imaging is to separate signal changes of other signal changes arising from stimulations or brain activitiesxe2x80x94caused by movements, for example. For this purpose, it has also been proposed to calculate a correlation coefficient for each pixel between the stimulation function and the received chronological signal curve. Periodically repeated stimulations that are separated by pauses are used as a stimulation function. Periodic stimulation functions, however, have a number of disadvantages:
Periodic disturbance processes (e.g heartbeat, respiration) cannot be separated from the activity signal and appear as xe2x80x9cphysiological noise.xe2x80x9d Processes showing a delay of integral multiples of the repetition period cannot be correctly recognized either. Prolonging this experiment does not lead to a better noise suppression in any of these cases.
Periodic stimulation functions have a nonuniform frequency spectrum. Therefore, specific spectral components are not or only weakly excited by the stimulation. This introduces a systematic error into the system identification, i.e.; the determination of the parameters of a mathematical model.
German Patent 195 29 639 suggests a method for the time-resolved and location-resolved representation of functional brain activities of a patient. A stimulation function stimulates physiological processes in a patient. The stimulation function is nonperiodic and has as a few as possible secondary maxima. On the basis of a pulse sequence for exciting and reading out nuclear magnetic resonance signals, time-resolved and location-resolved nuclear magnetic resonance signals are acquired and are converted into bits of image information. Time-resolved and location-resolved activity modifications in the patient are detected by the chronological correlation of the so acquired bits of information with the stimulation function.
The required MR data must be acquired as fast as possible with respect to the time and location resolution. Fast pulse sequences therefore are primarily used. The fastest currently available MR imaging sequence is referred to as EPI (echo planar imaging) sequence. Other fast pulse sequences such as turbo spin echo sequences, FISP or FLASH sequences are possible as well.
A high-frequency pulse is initially emitted in the EPI sequence. A slice selection gradient is simultaneously generated, so that only one slice of the examination subject is excited, dependent on the frequency spectrum of the high-frequency pulse and on the intensity of the slice selection gradient. A positive sub-pulse of the slice selection gradient is followed by a negative sub-pulse, with which the dephasing caused by the positive sub-pulse is reversed again.
At the same time as the negative sub-pulse of the slice selection gradient, two prephase pulses are emitted in a phase encoding direction or a readout direction.
The readout gradient, with alternating polarity, is subsequently activated. As a result of the alternating sign of the readout gradient, the nuclear magnetic resonance signals are repeatedly rephrased and a signal arises under each sub-pulse of the readout gradient.
The signals are respectively differently phase-encoded because the phase continues to switch from signal to signal by small phase encoding pulses between the signals.
The signals are phase-sensitively demodulated and are digitized in a matrix or grid. The received digital values are entered into a row of a raw data matrix for each signal. In the fastest version of the EPI method, referred to as xe2x80x9csingle-shot EPI,xe2x80x9d a sufficient number of signals are acquired after one single excitation in order to prepare a complete raw data set for an image. In a known way, the image can be acquired by two-dimensional Fourier transformation from the raw data matrix.
Not only spatial resolution but also a time resolution of the signals must occur for the functional imaging. For this purpose, the represented sequence is repeated as fast as possible, so that image data, which are allocated to different points in time, are successively received.
The smallest element of an image dataset is referred to as a pixel. A coarser resolution is generally sufficient for the functional imaging compared to conventional nuclear spin tomography images, such as a typical resolution of 256xc3x97256 pixels.
FIG. 5 herein shows the schematic process of the known method according to German Patent 195 29 639. The pulse sequence for exciting and reading out nuclear magnetic resonance signals AMR (k) and the stimulation function fS1 (k) run independently of one another. Both have an effect on the system 51 comprised of a human being and a magnetic resonance tomograph apparatus, and are clocked by a control computer (not shown); the pulse sequence AMR (k), however, is not triggered by the stimulation function fS1 (k). On the basis of the pulse sequence AMR (k), raw data sets SMR (k) are acquired and image data sets B (t), in turn, are acquired from said raw data sets by two-dimensional Fourier transformation 52. A chronological signal curve is received for each element in the raw data matrix SMR (k), or for each pixel in the image data matrix B (t). A cross correlation 54 subsequently ensues between this signal curve SMR (k), or B (t) and the stimulation function fS1 (k). The stimulation function fS1 (k) was subjected to a suitable delay element 53 having the delay T. It is not significant for the success of the method whether the cross correlation 54 is carried out with the raw data sets SMR (k) or the image data sets B (t), namely whether it is carried out before or after the Fourier transformation 52.
In order to avoid the aforementioned disadvantages, the stimulation function fS1 (k) is not allowed to be periodic and must be optimized with respect to the secondary maxima of its auto correlation function. For example, binary codes can be used.
The minimization of secondary maxima in the auto correlation function of such codes is equivalent to a flat performance spectrum and an optimal suppression of interference sources increasing with the length of the function. Additionally, the nonperiodicality can be seen in the minimization of secondary maxima in the auto correlation function. Influences of the stimulation can be extracted from the MR data by a cross correlation of such a stimulation function with the time-dependent function, as it is acquired for each pixel from the MR data. Disturbing processes such as movements (respiration, heartbeat, pulsating CSF) hardly occur during the cross correlation.
The result P1 (T) of the cross correlation 54 can be displayed at a monitor for each pixel. FIG. 6 herein schematically shows the chronological curve of the signal for each pixel. As already been explained in connection with FIG. 5, a connection between the stimulation function and the brain activities caused therewith is created by a correlation analysis. The result of this correlation analysis P1 (T) then can be represented again pixel by pixel at the monitor. Specific brain regions, i.e.; the allocated pixels, can be selected and the result of the correlation analysis can be viewed for this brain region.
An object of the present invention is to provide a method which allows fMRI experiments to be conducted with a number of parallel stimulation functions, to detect the activity changes in a life form under investigation, the activity changes being based on the number of stimulation functions, and to correctly allocate these to the initiating stimulation functions. Another object of the present invention is to provide a device for implementing the method.
The object is achieved in accordance with a first embodiment of the present invention in a method and an apparatus for the time-resolved and location-resolved representation of functional brain activities of a life form using nuclear magnetic resonance, wherein stimulation of physiological processes in the life form takes place with at least two non-correlating stimulation functions that are orthogonal to one another, and time-resolved and location-resolved nuclear magnetic resonance signals are generated by a pulse sequence for exciting and reading out nuclear magnetic resonance signals, and the generated nuclear magnetic resonance signals are cross-correlated stimulation functions for detecting activity changes in the life form that are based on the respective stimulation function.
Since the (at least) two stimulation functions do not correlate and therefore are oriented perpendicular to one another, it is possible, by means of the following chronological correlation of the nuclear magnetic resonance signals with the stimulation functions, to unambiguously allocate the linear activity change in the life form to a specific stimulation function, this activity change being due to one of the stimulation functions. In order to prevent runtime differences of the signals, the stimulation functions can proceed through suitable delay elements.
The inventive method makes it thus possible to carry out a number of fMRI experiments at the same time, i.e.; a fMRI experiment, wherein physiological processes are stimulated in the life form to be examined with at least two stimulation functions, without a mutual disturbance of the experiments. This saves considerable time and expense in respect to the implementation of the experiments.
In a second embodiment of the invention, physiological processes are stimulated in the life form with at least two non-correlating stimulation functions that are orthogonal to one another, time-resolved and location-resolved nuclear magnetic resonance signals are generated by a pulse sequence for exciting and reading out nuclear magnetic resonance signals, the generated nuclear magnetic resonance signals are correlated with a correlation function that is orthogonal to the stimulation functions, and the correlation function is varied for detecting activity changes in the life form that are based on non-linear coupling of the at least two stimulation functions.
Since the at least two stimulation functions do not correlate and therefore are oriented perpendicular to one another and since the correlation function is also orthogonal to the stimulation functions, it is inventively possible, by means of the chronological correlation of the nuclear magnetic resonance signals with a common correlation function being orthogonal to the stimulation functions, to detect the activity changes of higher order in the life form that are based on a combination of the stimulation functions. The correlation function is not necessarily a single specific function but stems from a family of functions fulfilling the aforementioned condition. Since the linear effects are suppressed during the correlation with the correlation function that is orthogonal to the stimulation functions, a signal received after the correlation can only be due to a nonlinear coupling of two or more stimulation functions. Since the correlation function, which has led to the result, is known a posteriori, it can be concluded a posteriori on which combination of stimulation functions the measured activity change in the life form is based. Moreover, disturb signals such as an unintended movement of the examined life form thus can be extracted. The correlation function can proceed through suitable delay elements here as well in order to eliminate runtime differences of the signals. The inventive method makes it thus possible to detect effects of higher order, i.e.; activity changes in the life form that react to the simultaneous existence of a number of stimuli (stimulation functions) and therefore are based on brain functions (referred to as higher brain functions) that are not accessible by direct stimulation using functional magnetic resonance tomography. A nonlinear coupling of the stimuli means that a brain region only reacts to the simultaneous existence of two stimuli, for example.
In both embodiments the inventive stimulation functions preferably are nonperiodic and have as few secondary maxima as possible in their auto correlation function. Particularly periodic disturbance signals, as a result of the heartbeat or the pulse sequence for exciting or reading out nuclear magnetic resonance signals, can be faded out by the chronological correlation of the signals.
It is in accordance with the invention to use advantageous binary codes as stimulation functions. This is particularly advantageous when the stimulation functions prescribe instructions for actions to be performed by the life form.
The binary codes allow a simple stimulation of the life form (clear signal-effect-relationship, e.g., xe2x80x9cMove small finger at light signalxe2x80x9d). Functions that are orthogonal to the stimulation functions can also be simply derived in a known way.
In order to exclude interactions between the pulse sequence for exciting and reading out nuclear magnetic resonance signals and the stimulation functions, in an embodiment of the invention, the pulse sequence and the stimulation functions are independent of one another.
In a further embodiment, for detecting a nonlinear coupling of two stimuli, the detection of activity changes in the life form based on nonlinear coupling of the (at least) two stimulation functions is carried out using statistic methods. The result of the cross-correlation is thereby evaluated using suitable statistic methods such as the xe2x80x9chigher order statistics,xe2x80x9d for example. These methods are particularly suitable for detecting and evaluating nonlinear terms in a signal.
The correlation function plays a significant role for detecting a nonlinear coupling of two stimuli. In an embodiment of the invention the correlation function is varied using a shift register. By using a shift register, a suitable family of functions can be produced, which are all perpendicular relative to the individual stimulation functions.